Our principal effort is directed to understanding the mechanisms by which novel DNA rearrangements occur in vivo. We have concentrated on two major systems: bacterial viruses capable of integration and excision and herpes simplex virus (HSV). Phage lambda is used for both in vivo and in vitro recombination systems and for cloning DNA fragments of HSV. We are studying the integration lambda into secondary sites on the E. coli genome. We can now screen lambda integration mutants for markedly altered integration patterns. We have isolated a lambda mutant that integrates at high frequenies in E. coli lacking the normal integration site. We are isolating specificity mutations in phage integration proteins, as well as deletions that define the control and structural regions of the lambda integration system. We are constructing plasmid chimeras in vitro that overproduce integration and excision proteins. We are investigating other bacterial systems with temperate viruses to further our insight into DNA integration mechanisms. We have cloned many fragments of the HSV genome in lambda and plasmids and are analyzing the structure of specific HSV fragments.